Interaction of small molecules (drugs) with biomembranes is known to modulate a variety of functions. However, the mechanism by which a solute modulates the biomembrane function remains to be determined. The potency of a series of drugs has been correlated in the past to their lipid solubility or to lipidic solvent/water (buffer) partition coefficient. Elsewhere (22) we have demonstrated that once the drug is incorporated into bilayer, it may modulate membrane function by modifying the phase transition behavior of the bilayer. One of the central questions in this study is whether lipidic solvent/water partition coefficient is correlated to mambrane/water coefficient. In this proposal I have concentrated on determining bilayer/water partition coefficients for phenothiazine tranquilizers and n-alkanols. This series of drugs is chosen for two reasons: considerable amount of data is available on their pharmacological potency and lipidic solvent/water partition coefficient. The partition coefficient data will be used for free energy correlations with the solute structure and for understanding the factors that determine abiility of a solute to modulate phase transition behavior of a bilayer.